Biology:Cathepsin E

From HandWiki
Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example
Cathepsin E
Identifiers
EC number3.4.23.34
CAS number110910-42-4
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum

Cathepsin E is an enzyme (EC 3.4.23.34) that in humans is encoded by the CTSE gene.[1][2][3] The enzyme is also known as slow-moving proteinase, erythrocyte membrane aspartic proteinase, SMP, EMAP, non-pepsin proteinase, cathepsin D-like acid proteinase, cathepsin E-like acid proteinase, cathepsin D-type proteinase) is an enzyme.[4][5][6][2]

Cathepsin E is a protease found in animals, as well as various other organisms, that belongs to the aspartic protease group. In humans it is encoded by the CTSE gene located at 1q32 on chromosome 1.[7][8][2][9] It is an intracellular non-lysosomal glycoprotein that is mainly found in the skin and in immune cells.[10] The protein is an aspartyl protease that functions as a disulfide-linked homodimer, and has an oligosaccharide chain of the high-mannose type.[11] It is a member of the peptidase A1 family, and therefore observes specificity similar to that of Pepsin A and Cathepsin D. Cathepsin E is an intracellular enzyme and does not appear to be involved in dietary protein digestion. It is found at highest abundance on the stomach’s epithelial mucus producing cell surfaces. It is the first aspartic protease present in the fetal stomach and is found in more than half of gastric cancers, leading to it appearing to be an oncofetal antigen. Transcript variants utilizing alternative polyadenylation signals and two transcript variants encoding different isoforms exist for this gene.[9][10]

A deficiency in the levels of Cathepsin E in the body may play a part in inflammatory skin diseases such as atopic dermatitis, for which treatment would rely on fixing functionality and levels of the protein in the body.[12] Along with renin and Cathepsin D, Cathepsin E is one of the only few aspartic proteases known to be made in human tissues other than those of gastrointestinal and reproductive tracts.[13]

Structure

The structure of Cathepsin E is very similar to those of Cathepsin D and BACE1, and all 3 have almost identical active site regions. The differences between them lie in the microenvironments that surround their active sites. Residues DTG 96-98 and DTG 281-283 contribute to the formation of the enzyme’s active site. There are also two pairs of disulfide bonds at residues Cys 272-276 and Cys 314-351. Two other Cys residues at positions 109 and 114 on the amino acid chain reside close to teach other in three dimensional space, however the distance between their sulfur atoms is 3.53 Å which is too large for the formation of a proper disulfide bond. The structure also has four hydrogen bonds between the Asp residues of the active site and the surrounding residues. A distinguishing factor of Cathepsin E in comparison with the structure of Cathepsin D and BACE1 can be seen at the formation of an extra hydrogen bond between the Asp 96 and Ser 99 residues, and absence of a hydrogen bond with Leu/Met at Asp 281.[12]

Location

The enzyme is distributed in cells of the gastrointestinal tracts, lymphoid tissues, blood cells, urinary organs and microglia. Its intracellular localization in different mammalian cells is different to that of its analog Cathepsin D. Cathepsin E associates with the membrane tissue in the intracellular canaliculi of gastric parietal cells, bile canaliculi of hepatic cells, cells of the rinal proximal tubule in the kidney, epithelial cells in the intestine, trachea and bronchi, osteoclasts and even in erythrocytes. Its localization in the endosome structures can be seen in many different cell types such as antigen-presenting B cell lymphoblasts, gastric cells and microglia. Its presence is also detected in the cisternae of the cell’s endoplasmic reticulum.[11][14]

Function

Cathepsin E plays a vital role in protein degradation, antigen processing via the MHC class II pathway[9] and bioactive protein generation. The enzyme is also thought to be involved in age induced neuronal death pathway execution as well as the excessive stimulation of glutamate receptors with excitotoxins and transient forebrain ischemia. In an experiment carried out on rats, Cathepsin E was barely detected in the brain tissues of young rats, however in older rats its level was greatly increased in the neostriatum and cerebral cortex. The enzyme was also expressed at high levels in the activated microglia of the hippocampal CA1 region and in degenerating neurons for a week after transient forebrain ischemia.[14] Cathepsin E has a possible role in the development of well differentiated adenocarcinoma from intestinal metaplasia.[11] The enzyme also plays a part in association with dendritic cells where it generates the CD4 repertoire in response to self and foreign proteins.[15]

Post-translational modification

The enzyme is glycosylated. Different cell types contribute to the differences in the nature of the carbohydrate chain. A high mannose-type oligosaccharide is observed in the proenzyme in fibroblasts, however the mature enzyme can be seen with a complex-type oligosaccharide. In the membranes of erythrocytes, the mature enzyme and the pro-enzyme both have a complex-type oligosaccharide. Auto catalytic cleavage produces two forms of the enzyme, with Form 1 beginning at residue Ile 54 and Form 2 at Thr 57.[16]

See also

References

  1. ↑ "Assignment of cathepsin E (CTSE) to human chromosome region 1q31 by in situ hybridization and analysis of somatic cell hybrids". Cytogenetics and Cell Genetics 53 (2–3): 137–9. Aug 1990. doi:10.1159/000132914. PMID 2369841. 
  2. ↑ 2.0 2.1 2.2 "Human gastric cathepsin E. Predicted sequence, localization to chromosome 1, and sequence homology with other aspartic proteinases". The Journal of Biological Chemistry 264 (28): 16748–53. October 1989. doi:10.1016/S0021-9258(19)84768-3. PMID 2674141. 
  3. ↑ "Entrez Gene: CTSE cathepsin E". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1510. 
  4. ↑ "Structural differences between rabbit cathepsin E and cathepsin D". Biological Chemistry Hoppe-Seyler 367 (6): 523–6. June 1986. doi:10.1515/bchm3.1986.367.1.523. PMID 3741628. 
  5. ↑ "Further studies on rat cathepsin E: subcellular localization and existence of the active subunit form". Archives of Biochemistry and Biophysics 267 (1): 176–83. November 1988. doi:10.1016/0003-9861(88)90021-5. PMID 3058036. 
  6. ↑ "Identification of the aspartic proteinases from human erythrocyte membranes and gastric mucosa (slow-moving proteinase) as catalytically equivalent to cathepsin E". The Biochemical Journal 254 (3): 895–8. September 1988. doi:10.1042/bj2540895. PMID 3058118. 
  7. ↑ "CTSE cathepsin E [Homo sapiens (human) - Gene - NCBI"]. https://www.ncbi.nlm.nih.gov/gene/1510. 
  8. ↑ "Assignment of cathepsin E (CTSE) to human chromosome region 1q31 by in situ hybridization and analysis of somatic cell hybrids". Cytogenetics and Cell Genetics 53 (2–3): 137–9. 1990. doi:10.1159/000132914. PMID 2369841. 
  9. ↑ 9.0 9.1 9.2 "Cathepsin E: a mini review". Biochemical and Biophysical Research Communications 367 (3): 517–22. March 2008. doi:10.1016/j.bbrc.2007.12.163. PMID 18178150. 
  10. ↑ 10.0 10.1 "Characterization of new fluorogenic substrates for the rapid and sensitive assay of cathepsin E and cathepsin D". Journal of Biochemistry 125 (6): 1137–43. June 1999. doi:10.1093/oxfordjournals.jbchem.a022396. PMID 10348917. 
  11. ↑ 11.0 11.1 11.2 "An immunocytochemical study on distinct intracellular localization of cathepsin E and cathepsin D in human gastric cells and various rat cells". Journal of Biochemistry 110 (6): 956–64. December 1991. doi:10.1093/oxfordjournals.jbchem.a123696. PMID 1794985. 
  12. ↑ 12.0 12.1 "Modeling the tertiary structure of human cathepsin-E". Biochemical and Biophysical Research Communications 331 (1): 56–60. May 2005. doi:10.1016/j.bbrc.2005.03.123. PMID 15845357. 
  13. ↑ "Generation of human endothelin by cathepsin E". FEBS Letters 273 (1–2): 99–102. October 1990. doi:10.1016/0014-5793(90)81060-2. PMID 2226872. 
  14. ↑ 14.0 14.1 "New functional aspects of cathepsin D and cathepsin E". Molecules and Cells 10 (6): 601–11. December 2000. doi:10.1007/s10059-000-0601-8. PMID 11211863. 
  15. ↑ "The expression and function of cathepsin E in dendritic cells". Journal of Immunology 174 (4): 1791–800. February 2005. doi:10.4049/jimmunol.174.4.1791. PMID 15699105. 
  16. ↑ "CTSE - Cathepsin E precursor - Homo sapiens (Human) - CTSE gene & protein". https://www.uniprot.org/uniprot/P14091. 

Further reading

External links



Retrieved from "https://handwiki.org/wiki/index.php?title=Biology:Cathepsin_E&oldid=3549916"